Our attempts to clarify the pathophysiological of seasonal affective disorder (SAD) & mechanisms of action of light therapy (LT), have shown blunted hypothalamo-pituitary-adrenal (HPA) responses to corticotrophin (CRH) & serotonin agonists m-CPP & ipsapirone; abnormally low circadian plasma prolactin levels & that light therapy reduces nocturnal core body temperature. Research conducted this past year follows. A) Experimental alteration of photoperiod affects pituitary gland volume (PGV), & PGV increases in non-seasonal depression. To assess whether PV changes among SAD patients (PTS) & controls (CTS), & across seasons, subjects underwent magnetic resonance imaging. There were no differences in PGV in PTS as compared to CTS, or across seasons. Independent of SAD, PGV increased in women but decreased in men winter to summer. B) Reduced density of beta- adrenergic receptors in leukocytes membrane preparations occurs in depressed patients (nonseasonal) & is correlated with depression severity suggesting a reduction in signal transduction. To assess whether the same occurs in PTS, we evaluated mononucleocyte G-proteins, which function in post receptor information transduction, & clinical state, in CTS & PTS with current SAD, &again at 2 & 8 weeks on LT. All measurements are now being repeated in summer, & data analysis will follow. C) PTS often overeat & gain weight, crave carbohydrates & have elevated glucose & insulin levels after glucose loan intake, features found with non-insulin resistance, we measured glycosylated hemoglobin (HbA1) levels. We predicted that PTS would have higher HbA1 levels as compared to CTS, & during winter found this to be so - but PTS levels were within a normal range. We are repeating measurements in summer to assess whether season affects HbA1 & relationship of HbA1 to summer symptom remission. D) Reduced core body temperature is observed across seasons but association with sleep architecture is unclear, as sleep has core temperature regulating functions. Nocturnal EEG & core, facial & hand temperatures were measured winter & summer. Results replicated our finding that PTS as compared to CTS had similar core & hand temperatures. There was no change in temperature across seasons in PTS or CTS. PTS had lower facial temperatures across seasons & facial temperatures decreased across seasons in both PTS & CTS. Reduced facial temperatures across seasons in PTS supports our hypothesis that light treatment & summer are related to decreased brain temperatures & possibly brain heat production. EEG data awaits analysis. E) Earlier we reported increased nocturnal TSH, T3, T4 and reverse T3 in PTS in winter, regardless of clinical status. In that study sample size was limited & the findings could reflect a shift in the rhythm of these variables rather than an absolute increase. Hence, we have drawn new samples throughout the night from 19 PTS & 19 CTS. Analysis is underway.